In early vertebrate development, apicobasally polarised blastomeres divide to produce inner non-polarised cells and outer polarised cells that follow different fates. How the polarity of these early blastomeres is established is not known. We have examined the role of Crumbs3, Lgl2 and the apical aPKC in the polarisation of frog blastomeres. Lgl2 localises to the basolateral membrane of blastomeres, while Crumbs3 localises to the apical and basolateral membranes. Overexpression aPKC and Crumbs3 expands the apical domain at the expense of the basolateral and repositions tight junctions in the new apical-basolateral interface. Loss of aPKC function causes loss of apical markers and redirects basolateral markers ectopically to the apical membrane. Cell polarity and tight junctions, but not cell adhesion,are lost and outer polarised cells become inner-like apolar cells. Overexpression of Xenopus Lgl2 phenocopies the aPKCknockout, suggesting that Lgl2 and aPKC act antagonistically. This was confirmed by showing that aPKC and Lgl2 can inhibit the localisation of each other and that Lgl2 rescues the apicalisation caused by aPKC. We conclude that an instrumental antagonistic interaction between aPKC and Lgl2 defines apicobasal polarity in early vertebrate development.

How the membrane environment informs when and where actin is polymerized in clathrin-mediated endocytosis is unclear. Daste et al. show that high membrane curvature stimulates PI(3,4)P2 dephosphorylation by INPP4A and that PI(3)P recruits SNX9 in conjunction with both PI(4,5)P2 and high membrane curvature. Furthermore, they find that Lowe syndrome mimics this membrane microenvironment with the aberrant formation of a PI(4,5)P2/PI(3)P intermediate, giving rise to actin comets.